Hemorrhagic vasculitis in children

Shenlaine-Henoch disease (hemorrhagic vasculitis, anaphylactoid purpura, hemorrhagic vasculitis, allergic purpura, haemorrhagic purpura Genocha, capillarotoxicosis) is a widespread systemic disease with a predominant lesion of the microcirculatory bed of the skin, joints, gastrointestinal tract, kidneys. The most vulnerable part of the terminal vascular bed is the postcapillary venules; The second place in terms of the degree of damage is the capillaries, the third - the arterioles. The microcirculatory bed of various organs, including skin, is affected.

[1], [2]

Epidemiology

The frequency of hemorrhagic vasculitis is 23-25 per 10 000 population; children from 4 to 7 years are more often sick, more often boys.

[3], [4], [5], [6], [7], [8], [9]

Causes of the hemorrhagic vasculitis in children

The causes of hemorrhagic vasculitis remain unclear. Some authors associate hemorrhagic vasculitis with various infections, others attach greater importance to the body's allergic mood, which, in the presence of chronic foci of infection (chronic tonsillitis, caries, tubing, etc.) leads to a decrease in immunity. Hemorrhagic vasculitis is a hyperergic vascular reaction to various factors, more often infectious (streptococcus and other bacteria, viruses, mycoplasma). In some cases, the development of the disease is preceded by vaccination, food and medicinal allergens, an insect bite, trauma, cooling, etc. Immediately the onset of the disease is often preceded by a viral or bacterial infection. Allergic reactions in the anamnesis, mainly in the form of food allergy or drug intolerance, are much less common. The role of hereditary factors is not excluded, so, the connection with HLA B35 is noted.

[10], [11], [12], [13]

Pathogenesis

In the pathogenesis of hemorrhagic vasculitis are important: hyperproduction of immune complexes, activation of the complement system, increased vascular permeability, damage to the vascular endothelium, hypercoagulation. At the base of vascular damage in this disease is generalized vasculitis of small vessels (arterioles, venules, capillaries) characterized by perivascular infiltration of granulocytes, endothelial changes and microthrombosis. In the skin, these injuries are limited to the vessels of the dermis, but extravasants reach the epidermis. In the gastrointestinal tract may be edema and submucosal hemorrhage, and erosive and ulcerative lesions of the mucosa are possible. In the kidneys, segmental glomerulitis and occlusion of capillaries with fibrinoid masses are noted; older lesions are characterized by the deposition of hyaline material and fibrosis. As a result, aseptic inflammation develops in microvessels with destruction of the wall, an increase in its permeability, triggers the mechanism of hypercoagulation, worsens the rheological properties of blood, possibly depletes the anticoagulant link of the coagulating system of blood, and shows free radical stress leading to tissue ischemia.

Patholography of hemorrhagic vasculitis (Shenlaine-Henoch disease)

In the skin, changes are localized mainly in the small vessels of the dermis in the form of leukoclastic vasculitis with extravasates of erythrocytes in the surrounding tissue. In the capillaries and other vessels, destructive changes in the walls of the type of fibrinoid necrosis often develop. Fibrinoid changes are also observed in collagen fibers surrounding the vessels. Sometimes necrosis of the vascular walls and surrounding collagen occurs, which leads to the closure of the lumen of the vessel. There is a perivascular infiltration, but often there is an infiltration of the walls of the vessels, consisting mainly of neutrophilic granulocytes and lymphocytes. Characteristic is karyorexis, or leukoclasia, with the formation of "nuclear dust". In some cases, diffuse infiltration of the upper parts of the dermis is determined against a background of pronounced edema and fibrinoid swelling with extravasates of erythrocytes. The epidermis in such cases also undergoes necrosis with the formation of ulcerative defects.

In chronic cases, necrobiotic changes and extravasation of erythrocytes are less pronounced. The walls of the capillaries are thickened, sometimes hyalineized, the infiltration consists mainly of lymphocytes with a small admixture of neutrophilic and eosinophilic granulocytes. As a rule, karyorexis is detected, which is an expression of anaphylactoid status. As a result of further changes in erythrocytes and their phagocytosis by macrophages, hemosiderin granules are detected in them.

[14], [15], [16]

Histogenesis of hemorrhagic vasculitis (Shenlaine-Henoch disease)

At the heart of the disease - deposition of IgA in the walls of the vessels of the skin and kidney glomeruli. In addition, fibrinogen and the C3 complement component are also found. In the serum of patients, an increase in the level of IgA and IgE was detected. Electron microscopic and immunological studies revealed that at the beginning of the endothelial cells of the affected capillaries adaptive changes occur: mitochondrial hypertrophy, intensive pinocytosis, increased lysosome number and active cytoplasmic transport, even phagocytosis. The presence of immune complexes in the lumens of the vessels causes aggregation of platelets on the surface of the endothelium and their migration through the wall. At the same time, platelets are damaged and vasoactive substances are released. Subsequently, neutrophilic granulocytes and tissue basophils that release vasoactive substances increase the damage to the vascular walls of the infiltrate cell.

Symptoms of the hemorrhagic vasculitis in children

Hemorrhagic vasculitis usually begins acutely, with a subfebrile, rarely febrile increase in body temperature, and sometimes without a temperature reaction. The clinical picture can be represented by one or more of the characteristic syndromes (cutaneous, articular, abdominal, renal), depending on which the simple and mixed forms of the disease are isolated.

Skin syndrome (purpura) occurs in all patients. More often at the onset of the disease, sometimes after the abdominal or other characteristic syndrome on the skin of the extensor surfaces of the extremities, mainly the lower ones, on the buttocks around the large joints there appears a symmetrical small-spotted or spotted-papular hemorrhagic rash. The intensity of the rash varies - from single elements to abundant, draining, sometimes in combination with angioneurotic edema. Eruptions are wavy, recurrent. Most hemorrhagic vasculitis begins with typical skin rashes - finely sporadic, symmetrically located elements, similar to bruises, do not disappear when pressed. Eruptions on the skin of the face, trunk, palms and feet are less frequent. With the extinction of the rash, pigmentation remains, in the place of which, with frequent relapses, peeling occurs.

Articular syndrome is the second most frequent symptom of hemorrhagic vasculitis. The degree of joint damage varies from arthralgia to reversible arthritis. Mostly large joints are affected, especially knee and ankle. Appear soreness, edema and changes in the shape of the joints, which last from several hours to several days. Stance deformation of the joints with a violation of their function does not happen.

Abdominal syndrome caused by edema and hemorrhages in the intestinal wall, mesentery or peritoneum, is observed in almost 70% of children. Patients may complain of mild abdominal pains that are not accompanied by dyspeptic disorders, do not cause special suffering and pass on their own or in the first 2-3 days from the start of treatment. However, often severe abdominal pains are paroxysmal, appear suddenly as colic, do not have a clear localization and last up to several days. There may be nausea, vomiting, unstable stool, episodes of intestinal and gastric bleeding. The presence of abdominal syndrome from the onset of the disease, the recurrent character of the pains require the joint observation of the patient by the pediatrician and the surgeon, since the pain syndrome in hemorrhagic vasculitis can be caused both by the manifestation of the disease and by its complication (intussusception, intestinal perforation).

Kidney syndrome occurs less frequently (40-60%) and in most cases does not occur first. It is manifested by hematuria of varying severity, less often by the development of glomerulonephritis (Shenlaine-Genocha nephritis), predominantly hematuric, but possibly nephrotic (with hematuria). Glomerulonephritis is morphologically characterized by focal mesangial proliferation with the deposition of immune complexes containing IgA, as well as the C3 component of complement and fibrin. Sometimes a diffuse mesangiocapillary glomerulonephritis is observed, in severe cases combined with extracapillary semilunium. With age, the frequency of kidney damage increases. The leading symptom of hemorrhagic vasculitis is moderate hematuria, usually combined with moderate proteinuria (less than 1 g / day). In the acute course in the onset of the disease, macrohematuria, which has no prognostic significance, may occur. Glomerulonephritis is more likely to be associated with the first year of the disease, less often during one of the relapses or after the disappearance of extrarenal manifestations of hemorrhagic vasculitis.

The course of hemorrhagic vasculitis is cyclical: a clearly delineated debut 1-3 weeks after acute viral or bacterial infection, vaccination and other causes and recovery in 4-8 weeks. Single observations of hemorrhagic vasculitis in children, which proceeds extremely hard in the form of fulminant purpura, are described.

Often, the course becomes wavy in nature with repeated eruptions (in the form of a monosyndrome or in combination with other syndromes), recurring for 6 months, rarely 1 year or more. As a rule, repeated waves of rashes in the presence of abdominal syndrome are accompanied by the appearance of renal syndrome.

The chronic course is peculiar to the variants with Shenlaine-Genocha nephritis or with isolated continuously recurrent skin hemorrhagic syndrome.

[17], [18], [19]

Forms

There is no accepted classification. In the working classifications of Shenlaine-Henoch disease, there are:

• phase of the disease (initial period, relapse, remission);
• clinical form (simple, mixed, mixed with kidney damage);
• basic clinical syndromes (cutaneous, articular, abdominal, renal);
• severity (light, moderate, severe);
• nature of the course (acute, prolonged, chronic recurrent).

[20], [21]

Diagnostics of the hemorrhagic vasculitis in children

The diagnosis of hemorrhagic vasculitis is determined by the nature of the acute skin syndrome, primarily due to the presence of a symmetrically located small-spotted hemorrhagic rash on the lower limbs. Difficulties arise if the first manifestation of the disease is pain in the joints, abdomen or changes in the analysis of urine. In these cases, the diagnosis is possible only with the subsequent appearance of a typical rash.

Laboratory diagnostics of hemorrhagic vasculitis

With a typical picture of hemorrhagic vasculitis in the analysis of peripheral blood there may be mild leukocytosis with neutrophilia, eosinophilia, thrombocytosis. In the absence of intestinal hemorrhage, the hemoglobin level and the number of erythrocytes are normal.

The general analysis of urine is changed in the presence of nephritis, transient changes in the urinary sediment are possible.

The system of blood coagulation in hemorrhagic vasculitis is characterized by a tendency to hypercoagulable, so the definition of the state of hemostasis should be the initial and subsequent for monitoring the adequacy of therapy. Hypercoagulation is most pronounced in severe course. To determine the status of hemostasis and the effectiveness of the prescribed treatment, the level of fibrinogen, soluble fibrin-monomer complexes, thrombin-antithrombin III complex, D-dimers, prothrombin F _w fragment and fibrinolytic activity of the blood should be monitored .

Wavy course of hemorrhagic vasculitis, the appearance of jade symptoms is the basis for determining the immune status, revealing a persistent viral or bacterial infection. As a rule, in children with hemorrhagic vasculitis, concentrations of C-reactive protein, IgA in serum are increased. Immunological changes in the form of an increase in the level of IgA, CEC and cryoglobulins are more often accompanied by recurrent forms and nephritis.

Biochemical blood analysis has an applied value, only when the kidneys are affected, the level of nitrogenous slag and potassium serum is detected.

[22], [23]

Instrumental methods for hemorrhagic vasculitis

According to the indications prescribe ECG, chest X-ray, ultrasound of the abdominal cavity organs. The appearance of signs of kidney damage is the basis for ultrasound of kidneys, dynamic nephroscintigraphy, as often these children are diagnosed with anomalies of the development of the urinary system, signs of kidney dysembryogenesis, impairment of accumulative and excretory functions of the kidneys. These results allow predicting the course of nephritis in Shenlen-Henoch disease, monitoring treatment, persistence of glomerulonephritis manifestations, despite ongoing therapy, an indication for a kidney biopsy.

Differential diagnosis

Differential diagnosis of hemorrhagic vasculitis should be carried out firstly with diseases that are characterized by hemorrhagic purpura: infections (infectious endocarditis, meningococcemia), other rheumatic diseases, chronic active hepatitis, tumors, lymphoproliferative diseases, many of these diseases occur with joint and kidney damage.

The presence of a small (petechial) rash can cause suspicion of thrombocytopenic purpura, but for Shenlaine-Henoch disease typical typical localization of the rash (on the buttocks, lower extremities), with no thrombocytopenia.

Abdominal syndrome with hemorrhagic vasculitis should be distinguished from diseases accompanied by a picture of the acute abdomen, including acute appendicitis, intestinal obstruction, perforated stomach ulcer, yersiniosis, ulcerative colitis. In favor of the Shenlaine-Henoch disease, cramping pains, at the height of which there are bloody vomiting and melena, and concomitant skin changes, articular syndrome. With the prevalence of gastrointestinal symptoms, the clinical picture may resemble a picture of an acute abdomen, therefore, when examining each patient with acute pain in the abdomen, one should remember about hemorrhagic vasculitis and seek concomitant rashes, nephritis or arthritis.

With severe kidney damage, there may be an assumption about acute glomerulonephritis, in the differential diagnosis helps to identify other manifestations of hemorrhagic vasculitis. If the patient suffers from a chronic kidney disease, it is necessary to find out whether he had had a hemorrhagic vasculitis in his past. Renal forms of the disease should be differentiated first of all from IgA-nephropathy, which proceeds with recurrences of macrogematuria or microhematuria.

Differential diagnosis with other rheumatic diseases rarely causes difficulties. The exception is systemic lupus erythematosus, which in its debut may have symptoms of hemorrhagic vasculitis, but at the same time identify immunological markers (antibodies to DNA, ANF) that are not characteristic of hemorrhagic vasculitis.

Treatment of the hemorrhagic vasculitis in children

Indications for hospitalization are the debut, recurrence of hemorrhagic vasculitis.

Non-drug treatment of hemorrhagic vasculitis

In the acute period of hemorrhagic vasculitis, hospitalization, bed rest for skin rash, hypoallergenic diet are mandatory. Bed rest is necessary to improve blood circulation until the rash and pain disappear and then gradually expand it. Violation of bed rest often leads to increased or repeated rashes. Hypoallergenic diet with the exception of obligate allergens (chocolate, coffee, cocoa, citrus fruits - lemons, oranges, grapefruit, tangerines, chicken, chips, carbonated color drinks, nuts, dried crusts, all red fruits and vegetables) is indicated to all patients in an acute period. With severe pain in the abdomen, table No. 1 is prescribed (antiulcer). In the nephrotic variant of glomerulonephritis, a salt-free diet with protein restriction is used.

Medication for hemorrhagic vasculitis

Medical treatment is carried out taking into account the phase of the disease, the clinical form, the nature of the main clinical syndromes, the severity, the nature of the course.

Criteria for severity of hemorrhagic vasculitis:

• light - satisfactory health, ungrowth, rheumatoid arthralgia;
• moderate severity - profuse rashes, arthralgia or arthritis, periodic abdominal pain, microhematuria, trace proteinuria;
• heavy - rashes abundant, draining, elements of necrosis, angioedema; persistent abdominal pain, gastrointestinal bleeding; macrohematuria, nephrotic syndrome, acute renal failure.

Medication consists of pathogenetic and symptomatic.

Pathogenetic therapy of hemorrhagic vasculitis according to the nature and duration depends on the localization of vascular lesion and its severity. For treatment use heparin sodium in an individually selected dose. In almost all cases, antiaggregants are prescribed, according to indications - activators of fibrinolysis. Moreover, if the treatment is easy with only antiaggregants, then with moderate and severe forms, a combination of anticoagulants with antiplatelet agents is necessary. Glucocorticosteroids are prescribed for severe disease and with Shenlaine-Genocha nephritis. Of drugs with an immunosuppressive effect in nephritis, cyclophosphamide, azathioprine, 4-aminoquinoline derivatives are prescribed. In the case of acute or exacerbation of chronic foci of infection, antibiotics are used; if the infection process supports the recurrence of hemorrhagic vasculitis, immunoglobulins for intravenous administration are included in the treatment package.

Below are indications for the purpose and methods of using pathogenetic methods for the treatment of hemorrhagic vasculitis.

• Antiaggregants are all forms of the disease. Dipyridamole (curantyl, persanthin) at a dose of 5-8 mg / kg per day in 4 divided doses; pentoxifylline (trental, agapurin) 5-10 mg / kg per day in 3 doses; ticlopidine (tiklid) 250 mg twice a day. In severe course, two drugs are prescribed simultaneously to enhance the antiaggregant effect. Activators fibrinoliza - nicotinic acid, xanthinal nicotinate (theonikol, komplamin) - the dose is selected taking into account the individual sensitivity, usually it is 0.3-0.6 g per day. The duration of treatment depends on the clinical form and severity: 2-3 months - with an easy flow; 4-6 months - with an average; up to 12 months - with a severe recurrent course and Shenlaine-Genocha nephritis; in chronic course, repeat courses for 3-6 months.
• Anticoagulants - an active period of medium and heavy forms. Apply heparin sodium or its low-molecular analogue - calcium supraparin (Fraxiparin). A dose of sodium heparin is selected individually depending on the severity of the disease (on average 100-300 units / kg, less often - higher doses), focusing on the positive dynamics and coagulogram indices. With an average course of treatment usually lasts up to 25-30 days; at severe - to persistent relief of clinical syndromes (45-60 days); with hemorrhagic vasculitis nephritis, the duration of heparin therapy is determined individually. Drugs are canceled gradually at 100 units / kg per day every 1-3 days.
• Glucocorticosteroids - a severe course of cutaneous, articular, abdominal syndromes, kidney damage. With a simple and mixed form without kidney damage, the dose of prednisolone is 0.7-1.5 mg / kg per day in a short course (7-20 days). With the development of jade Shenlene-Genocha appoint 2 mg / kg per day for 1-2 months, followed by a decrease of 2.5-5.0 mg 1 time in 5-7 days before cancellation.
• Cytostatics - severe forms of jade, skin syndrome with necrosis on the background of high immunological activity. Derivatives of 4-aminoquinoline - with the extinction of severe symptoms against a background of a decrease in the dose of prednisolone or after its withdrawal.
• Antibiotics - intercurrent infections in the debut or against the background of the disease, the presence of foci of infection.
• IVIG is a severe, continuously recurring course of the disease associated with bacterial and / or viral infections that are not amenable to sanation. IVIG is administered at a low and an average exchange rate (400-500 mg / kg).

Symptomatic treatment of hemorrhagic vasculitis includes infusion therapy, antihistamines, enterosorbents, NSAIDs. In the treatment of recurrent forms, special attention should be paid to the search for a possible cause that supports the pathological process. Most often, these are infectious factors, so the sanation of foci of infection often leads to remission.

In severe hemorrhagic vasculitis during an acute period, intravenous injection of dextran (reopoliglyukin), glucose-novocaine mixture (in a ratio of 3: 1) is used. Antihistamines are effective in children who have a history of eating, drug or household allergies, manifestations of exudative-catarrhal diathesis, allergic diseases (pollinosis, Quincke edema, obstructive bronchitis, bronchial asthma). Use klemastin (tavegil), chloropyramine (suprastin), mebhydroline (diazolin), hifenadin (fenkarol) and other drugs in the dose levels for 7-10 days. Enterosorbents [lignin hydrolyzed (polyphepan), smectite dioctahedral (smecta), povidone (enterosorb), activated charcoal 3-4 times a day for 5-10 days] are necessary for patients with a burdened allergological anamnesis in cases when food agents served as a provoking factor of the disease . Enterosorbents bind toxins and biologically active substances in the intestinal lumen, thereby preventing their penetration into the systemic bloodstream. NSAIDs are prescribed a short course in case of severe articular syndrome.

Surgical treatment of hemorrhagic vasculitis

Surgical treatment (laparoscopy, laparotomy) is indicated in the development of symptoms of an "acute abdomen" in a patient with abdominal syndrome. In addition, during the period of remission according to the indications (chronic tonsillitis), tonsillectomy is performed.

Indications for consultation of other specialists

• The surgeon is a pronounced abdominal syndrome.
• ENT, dentist - pathology of ENT organs, necessity of teeth sanitation.
• Nephrologist - Shenlaine-Genocha nephritis.

Prevention

Primary prophylaxis of hemorrhagic vasculitis has not been developed. Prevention of exacerbations and relapses of Shenlaine-Henoch disease consists in preventing exacerbations, sanation of foci of infections, refusal to take antibiotics, eliminating contact with allergens, provoking factors - cooling, physical stress, stressful situations.

[24], [25],

Forecast

The outcome of hemorrhagic vasculitis is generally favorable. Recovery after the debut is noted in more than half of patients. Perhaps a long-term recurring course of the disease, with the frequency of relapses ranging from single for several years to monthly. With the development of abdominal syndrome, surgical complications are possible (intussusception, intestinal obstruction, perforation of the intestine with the development of peritonitis). Shenlaine-Genocha nephritis can be complicated by renal insufficiency of the acute period. The prognosis determines the degree of kidney damage, as a result of which chronic renal failure may develop. An adverse prognosis of hemorrhagic vasculitis is associated with the presence of nephrotic syndrome, arterial hypertension and extracapillary proliferation in the form of semi-moons.

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